tbuckley/cabot-search huggingface dataset:
Detection effectiveness of immune-related gene mutations in lung adenocarcinoma by circulating tumor DNA.
Authors: Jing Qin, Fengxiang Yin, Weifeng Guo, Guoying Zhang, Shasha Du, Danni Liu, Zhang Jing, Shaochen Cheng
Journal: Journal of Clinical Oncology (2023)

e20580 Background: Lung adenocarcinomas (LUAD) is the major pathological subtype of lung cancer with a poor prognosis. Tumor development and progression are significantly influenced by immune microenvironment. However, immune-related gene alterations have not been utilized in prognostic evaluation frequently. Circulating tumor DNA (ctDNA) provides a non-invasive approach to cancer diagnosis and prognosis. It is possible to find immune-related biomarkers that may be used to predict clinical outcomes and evaluate the effectiveness of ctDNA for the detection of immune-related gene mutations in LUAD. Methods: Immunologically relevant genes were downloaded from ImmPort, including chemokines (n = 102), cytokine receptors (n = 307), cytokines (n = 456), interferons (n = 17), interleukins receptors (n = 42), interleukins (n = 47), TGF-β family (n = 33) and TNF family (n = 12). Clinical and genetic mutation data of 604 LUAD samples were obtained from cBioPortal. The Kaplan-Meier method of survival analysis was used to estimate the overall survival (OS) of the published LUAD data set. 1837 LUAD patients collected both tumor tissue and blood samples were screened from the HapLab database (HaploX, Shenzhen, China). Results: OS analysis had been processed in each immune-related gene set and gene receptively. Only patients with cytokine receptor mutations showed a poor prognosis compared with the wild-type (log-rank test, p-value = 0.027). OS did not differ statistically significantly in patients with or without alterations in any other immune-related gene sets or individual genes. Protein-coding mutations of 32 cytokine receptor genes were found in 1290 LUAD tumor tissue samples from HapLab database. 93.75% (30/32) genes were observed mutations in paired plasma ctDNA results, and the minimum variant allele frequency (VAF) was 0.04%. 243 alterations in cytokine receptor genes were only detected in 54 peripheral blood samples. The overall sensitivity and specificity were 91.09% and 40.05% in blood ctDNA assay. Conclusions: The mutational status of cytokine receptor genes in LUAD is significantly associated with long-term OS. The presence of tumor DNA in the blood showed high diagnostic accuracy for detecting cytokine receptor mutations in LUAD patients. Circulating tumor DNA-based liquid biopsy offers LUAD patients a non-invasive prognostic assessment method based on immune-related gene mutation screening. [Table: see text]
Association of molecular profiles of head and neck squamous cell carcinoma with heterogeneity across racial/ethnic groups in the United States.
Authors: Mihir K Bhayani, Ellen B. Jaeger, Samer Al-Khudari, Kerstin Stenson, Nikhil Joshi, Jen Godden, Melissa Conrad Stoppler, Michael J. Jelinek
Journal: Journal of Clinical Oncology (2023)

e18036 Background: Significant disparities exist across the head and neck cancer (HNC) care continuum in presentation, treatment, and survival. Along with demographic factors such as race or ethnicity, tumor-specific molecular signatures may play a role in these differences. In the United States, the current body of literature mainly highlights molecular contrasts between Black and White patients. Here, we further investigate the molecular profiles of Black and White patients with HNC and add to the literature by comparing additional racial/ethnic groups in a large, real-world cohort. Methods: De-identified records of patients with a primary diagnosis of HNC who underwent Tempus xT testing (Tempus Labs, Chicago, IL) were selected from the Tempus Database. Those with squamous cell histology and self-reported race were selected for retrospective analysis. Briefly, Tempus xT is a targeted, tumor/normal-matched panel that detects single-nucleotide variants, insertions and/or deletions, and copy number variants in 648 genes, as well as chromosomal rearrangements in 22 genes with high sensitivity and specificity. Tumor mutational burden (TMB) was calculated by dividing the number of nonsynonymous mutations by the megabase size of the panel. Results: Among the 749 patients included, most identified as Non-Hispanic/Latino (NHL) White (n = 570), while 62 identified as NHL Black, 44 as NHL Asian/Pacific Islander (API), 21 as NHL of other races, and 52 as Hispanic/Latino of any race. Age at diagnosis differed between races ( P= 0.009). Oral cavity was the most common subsite in our cohort (N = 306, 41%). TMB also differed among races ( P= 0.018), with Black patients demonstrating the highest TMB (median = 4.6 mut/Mb [3.0-6.2]) and API the lowest (median = 2.3 mut/Mb [1.5-4.2]). Black patients had higher proportions of TP53 (76%), KMT2D (24%), and CTTN (15%) alterations (not significant across races). There were differences in the frequencies of OR4G11P (q = 0.031) and OR4F5 (q = 0.014) aberrations between races, with Black patients showing the highest frequencies (16% and 15%, respectively). The API population demonstrated higher frequencies of RASA1 (16%), MTAP (11%), CDKN2B (32%), and ERCC3 (11%) mutations (not significant across races). Additionally, there were differences in TERT mutations between races (q = 0.01), with API harboring the highest proportion of TERT co-mutations (52%). Conclusions: Overall, these results demonstrate that molecular profiles are heterogeneous across multiple racial/ethnic groups. Many of the alterations described here have been previously associated with outcomes in HNC. Accordingly, future investigations should aim to understand the effects of the activated pathways for clinical utility and investigate biomarkers to drive individualized treatment plans that result in equitable care.
Gynecologic oncology patients’ perception of physician empathy in the age of COVID-19.
Authors: Gavriel Cohn, Bradford Whitcomb
Journal: Journal of Clinical Oncology (2023)

e24186 Background: Since the beginning of the COVID-19 pandemic there have been major changes to the medical office experience, including universal masking. Prior studies had shown that the environmental layout 1 , the ability of the patients to see the physician’s face 2 , as well as the interactions with other office staff members 3 , as well as the length of the patient-physician relationship 4 all played into the patient’s perception of physician empathy and that this perceived. Because establishing care during the pandemic would undercut many of these known factors, it was hypothesized that those who established care after the onset of the pandemic would have lower scores on the Jefferson scale of Physician empathy (JSPE) and European Quality of life survey (EQ-5D™). Methods: Patients of the Carole and Ray Neag Cancer Center department of Gynecologic Oncology at UConn Health were surveys at the time of their appointments. Sampling occurred between June and November of 2022. Surveys collected demographic information including age, stage of cancer, and number of visits since the onset of the pandemic in March 2020; the JSPE along with questions directly related to care during the pandemic scored the same way; the EQ-5D™; and a checkable list of changes noted in the office. The results of the “Pre-COVID” and “Post-COVID” cohorts were compared using a two-group t-test for statistical significance. An n of 30 per cohort was needed for a power of &gt; 80%. Results: Results showed that patients who had established care prior to the pandemic (n = 29) were more likely to be seen while in remission while those who established care after the onset of the pandemic (n = 33) were more likely to be seen for postoperative surgical care or an active cancer. Patients who established care prior to the pandemic had statistically significantly lower scores on the JSPE than those who did not (6.08 +/- 2.00 vs 6.73 +/- 0.71 p = &lt; 0.001). However, individuals who established care prior to the pandemic had statistically higher qualities of life as measured by the EQ-5D™ compared to those who established care after the onset of the pandemic (4.57 +/- 0.72 vs 4.22 +/- 0.85 p = &lt; 0.001). There was no statistically significant difference in the number of changes notes (4.483 +/- 1.57 vs. 5.09 +/- 1.38 p = 0.189). Conclusions: While statistically significant differences between the cohorts were found, the overlapping standard deviations, the fact that the JSPE and EQ-5D™ went in separate directions, and the generally favorable responses lead to the conclusion that the differences were not clinically significant. This means that, contrary to research conducted prior to widespread masking and the COVID-19 pandemic, providers are still able to be perceived as empathetic and provide quality care to their patients despite the changes that have taken place in the medical office setting since the onset of the pandemic.
Comprehensive genetic characteristics of multiple primary lung cancer in patients in China.
Authors: Guotian Pei, Yingshun Yang, Mingwei Li, Xiaoxue Ma, Jiayue Qin, Shanbo Cao, Qiang Liu, Shuai Wang, Yuqing Huang
Journal: Journal of Clinical Oncology (2023)

e20597 Background: With the development of molecular biology and next-generation sequencing (NGS), researchers have been exploring the use of genomic technologies for the classification of lung cancers. The aim of this study was to investigate genetic characteristics of multiple primary lung cancer (MPLC) to facilitate precise diagnosis and therapy by NGS. Methods: A total of 271 lesions from 92 patients with MPLC (225 lesions) and 20 intrapulmonary metastasis (IM, 46 lesions) which were diagnosed by American College of Chest Physicians (ACCP) guidelines, were sequenced by Acornmed panel with 808 cancer-related genes. Results: The most frequent mutation in 225 lesions was EGFR (46.7%), followed by RBM10 (19.6%), BRAF (16.4%) and KRAS (15.1%) among MPLC while IM lesions showed high TP53 (63.0%) mutation frequency. Further analysis showed that MPLC patients had higher proportion of private mutations, and lower proportion of shared mutations and branch shared mutations than IM (p &lt; 0.0001). In our cohort, 95.7% (88/92) of MPLC patients had at least one driver alteration, and EGFR and KRAS comprised 57.4% and 18.0% of 183 driver mutations, respectively. Further analysis showed that only 19.6% (18/92) of MPLC shared the same driver mutation in each patient and 61.1% (11/18) of co-driver mutation was EGFR L858R which was commonly detected in lung cancer. In contrast, 95.0% (19/20) of IM shared the same driver mutation in each patient. MPLCs were associated with a high frequency of T &gt; C transitions (p &lt; 0.001), while T &gt; G transversions (p &lt; 0.001) were more frequent in tumors from IM. MPLC had significantly higher intratumor heterogeneity (ITH) (17.1 vs 4.05, p &lt; 0.001) and lower weighted-genomic integrity index (wGII) than IM (0.01638 vs 0.18321, p &lt; 0.001). Besides, MPLC had lower percentage of clonal mutations (p &lt; 0.001) than IM. However, IM had higher arm-level somatic copy number variations fraction (p &lt; 0.001) than MPLC. Conclusions: Our analysis reveals that patients with MPLC have distinct molecular characteristics different from IM, which may increase the understanding of MPLC. In addition, the molecular features of MPLC may provide new opportunities to distinguish MPLC from IM by broad panel NGS.
A comparison of thyroid cancer survival managed with different surgical subtypes: A SEER database analysis.
Authors: Laura Cogua, Peter T. Silberstein, Connor Tupper
Journal: Journal of Clinical Oncology (2023)

e18110 Background: Thyroid cancer is a common endocrine malignancy that has been shown to be treatable with surgical intervention. Multiple surgical approaches can be used to treat thyroid cancer ranging from minimally-invasive local destruction or partial lobectomy to total thyroidectomy. There are limited studies comparing the survival between different surgical subtypes used to treat thyroid cancer at a national registry level; we herein investigate the differences between surgical subtypes in the management of thyroid cancer. Methods: We queried the Surveillance, Epidemiology, and End Results (SEER) Database for patients with thyroid cancer (primary site code C739) diagnosed between 2000-2019. All histologic subtypes were included. Patients with multiple primary tumors and patients without surgical intervention were excluded. Variables selected for review included age at diagnosis, race, sex, stage, and surgery subtype. Surgical subtypes of interest included codes 20-50 which corresponds to the removal of less than a lobe NOS, local surgical excision, partial lobectomy, lobectomy only, isthmectomy only, lobectomy with isthmectomy, removal of a lobe and partial removal of the contralateral lobe, subtotal or near-total thyroidectomy, and total thyroidectomy. Descriptive statistics, Kaplan-Meier (KM), and Cox regression analyses were performed using SPSS version 28. Results: A total of 167932 patients were included. Of these, 1564 patients received local/partial lobectomy. On KM, partial lobectomy showed significantly improved survival compared to both local excision and removal of less than a lobe, NOS (p’s &lt; 0.05). For lobectomies and isthmectomies, a total of 24904 patients were included. On KM, both lobectomy alone and lobectomy with isthmectomy showed survived significantly improved than isthmectomy alone (p’s &lt; 0.001). A total of 141464 patients received either subtotal thyroidectomies or total thyroidectomies, 95% of which were total thyroidectomies. On KM, patients managed with total thyroidectomy survived significantly better than subtotal thyroidectomy (p &lt; 0.001). After controlling for age, sex, race, and stage, Cox regression analysis showed complete lobectomy (Hazard ratio [HR] = 0.352), subtotal thyroidectomy (HR = 0.416), and total thyroidectomy (HR = 0.162) all had significantly improved survival relative to local excision or destruction (p’s &lt; 0.001). Conclusions: Our results show that more complete removal of the thyroid, including complete lobectomy, subtotal thyroidectomy, and total thyroidectomy, is associated with improved survival in patients with thyroid cancers. The improved outcomes with more invasive procedures suggest wider margins may reduce the risk of spread or recurrence after initial resection.
Racial disparities and inequity in clinical trials of chimeric antigen receptor T-cell therapy.
Authors: Rahul Kumar Thakur, Ansh Mehta, Charan Thej Reddy Vegivinti, M Bakri Bakri Hammami, Biplov Adhikari, Roshan Subedi, Anurag Adhikari, Abhishek Kumar
Journal: Journal of Clinical Oncology (2023)

e18515 Background: Chimeric antigen receptor (CAR) T-cell therapy is a paradigm-shifting advancement in hematologic malignancies with therapeutic futility. There is growing evidence that there are disparities affecting race and ethnicity for malignancy treatments as well as under-representation of minorities in clinical trials. We analyzed the racial representation in clinical trials of CAR-T products in the US. Methods: We searched all clinical trials in PubMed for six FDA-approved CAR-T therapy for all indications. We included all phase 2 and above published trials that were conducted in the US and recorded demographic data. Results: Out of total 64 studies; 16 were included for final analysis. A total of 1678 patients enrolled in the CAR-T therapy trials. The table shows indication and demographic data of the patient. Only 9 (56%) articles reported race and 8 (50%) articles reported ethnicity. We found only 47 (3%) African Americans, 47 (3%) Asian races, and 53 (3%) Hispanic ethnicity patients were enrolled in the trials. Conclusions: Our study highlights inadequate reporting of race/ethnicity and continued under-representation of minorities in clinical trials. This is the largest study examining the generalizability of CAR-T cell therapy RCTs at a population level. The underrepresentation in RCTs is an alarming finding as the incidence of many of the diseases is quite high in such minority populations thus exposing a significant disparity in health equity and healthcare access. More insights through research and policymaking are necessary to overcome barriers to delivering equitable healthcare, especially to underrepresented minorities.[Table: see text]
Study for the prevention of oral mucositis.
Authors: Artem Oganesyan, Lusine Harutyunyan, Araksya Vanoyan, Nare Martirosyan, Maria Badikyan, Nerses Ghahramanyan, Hasmik Oseyan, Levon Evoyan, Armine Farmazyan, Amalya Chakhoyan, Hayk Grigoryan, Anahit Ter-Grigoryan, Anna Sevoyan, Avetis Gharibyan, Anahit Aynajyan, Karapet Hakobyan, Yervand Hakobyan
Journal: Journal of Clinical Oncology (2023)

TPS12149 Background: Oral mucositis (OM) is a serious complication of cancer treatments characterized by erythema and ulcerations of the mouth. Consequences of OM include pain, diminished functionality, and infections leading to decreased quality of life and discontinuity in therapy. About 20-40% of patients receiving chemotherapy develop OM within 7 days of treatment initiation. Current clinical guidelines recommend prophylactic oral care, cryotherapy, KGF-1, palifermin, and photobiomodulation to prevent OM in specific patient groups. Benzydamine is approved for the prevention of OM in head and neck cancer patients receiving radiotherapy or radio-chemotherapy but has not been well studied for chemotherapy alone. The effectiveness of oral topical treatments is limited by dilution in the saliva and swallowing shortening the duration of their action. Bocaliner is a novel medical device that is hypothesized to enhance the effects of treatments by prolonging the oral retention of topical therapies within the oral cavity. Methods: The Study for the Prevention of Oral Mucositis (SPOM) is a randomized controlled Phase I/II trial that aims to evaluate the efficacy of two different tools (benzydamine mouthwash and Bocaliner) in reducing the incidence and severity of OM in patients undergoing systemic chemotherapy (NCT05338398). A total of 100 adult patients with hematologic malignancies undergoing chemotherapy in a centralized hematology center in Armenia will be randomized into two different treatment groups: saline mouthwash and benzydamine mouthwash (0.15%, 120mL) 3-5 times a day for a total of two weeks. Half of the patients within each group will also randomly receive Bocaliner, which will be placed inside of their mouth immediately after the application of the mouthwash for 20 minutes. Block randomization will be applied with 4 patients per block with 1:1 randomization based on gender, Bocaliner use, and mouthwash type. The primary endpoint is the difference in OM incidence measured by the WHO Oral Toxicity Scale. The secondary endpoints are differences in OM symptoms evaluated using a modified version of the PROMS questionnaire. Safety and tolerability of the medical device will be determined for the Phase I component of the study based on responses to standardized tryout (Day 0) and follow-up questionnaires (Day 14). Other outcomes include the duration and severity of OM. Statistical analysis will explore further clinically meaningful associations between patient data, received therapies, and outcomes. Forty-two patients have already completed the study, while the enrollment of other participants continues and is planned to be completed by the end of 2023. Clinical trial information: NCT05338398 .
Overall survival in treated ovarian cancer patients in Argentina: OCEANIA study.
Authors: Gabriela Abreu, Juliana Queiroz, Thiago Nogueira, Claudia Soares, Patricia Menezes, Mariano Nicolas Carrizo, Juan Criniti, Rosana Felice, Paula Scibona, Ventura Simonovich, Maria Cecilia Riggi, Florencia Cravero, Diego Odetto, José Saadi, Laura Fabia Jotimliansky
Journal: Journal of Clinical Oncology (2023)

e17595 Background: OCEANIA is a retrospective, real-world database study that evaluated treatment patterns and outcomes in a cohort of patients diagnosed with ovarian cancer (OC) in private healthcare settings in Latin America. The present analysis focused on evaluating up to five-year overall survival (OS) in a cohort of treated patients with OC in Argentina. Methods: Patients with an OC code diagnosed from 2010 to 2019 and with a cancer-related treatment claim (antineoplastics, surgery, and/or radiotherapy) were selected from a private healthcare provider’s database (Hospital Italiano de Buenos Aires) in Argentina. Patients were followed from diagnosis until the end of observation period or death. Frequency of OC patients by FIGO (International Federation of Gynecology and Obstetrics) stage was described. Cumulative treatment type was described through the whole follow-up period. One- to five-year survival Kaplan–Meier curves were built; patients who were lost to follow-up were censored. Results: 741 patients with OC were identified in the database with a mean (standard deviation) follow-up time of 31.7 (30.6) months; 539 (72.7%) were treated during this period. Among this population, 76.3% had information about FIGO staging: 73 (17.8%) were stage 1; 36 (8.8%) stage 2; 259 (63.0%) stage 3; and 43 (10.5%) stage 4. Cumulative distribution across treatment types revealed 355 (65.9%) patients received antineoplastics (321 [90.4%] received platinum-based treatment), 496 (92.0%) surgery and 18 (3.3%) radiotherapy. During a five-year observation window, 111 patients died (more than one half within two years of diagnosis). The adjusted cumulative OS for all treated patients in years 1–5 was 93.2%, 87.2%, 80.9%, 74.1%, and 69.0%, respectively (Table). Conclusions: OS is a key outcome in assessing the impact of current standards of care. Based on the results, although most (69.0%) of the patients survived after 5 years of follow-up, further improvement in OS presents a challenge. However, recent drug releases for OC management in Latin America may change this scenario. [Table: see text]